Characterization of T cell phenotype and function in a double transgenic (collagen-specific TCR/HLA-DR1) humanized model of arthritis.
Characterization of T cell phenotype and function in a double transgenic (collagen-specific TCR/HLA-DR1) humanized model of arthritis.
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DOI：
10.1186/ar4433
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发表时间：
2014-01-10
影响因子：
4.9
通讯作者：
Myers LK
中科院分区：
文献类型：
--
作者：
Tang B;Kim S;Hammond S;Cullins DL;Brand DD;Rosloniec EF;Stuart JM;Postlethwaite AE;Kang AH;Myers LK
T细胞在类风湿性关节炎（RA）中协调关节炎症，但由于抗原特异性细胞数量较少，因此难以研究。本研究的目标是描述一种新的自身免疫性关节炎人源化模型的特征，并描述诱导病理事件后自身免疫T细胞中发生的表型和功能变化。我们开发了一种含有HLA-DR 1转基因和HLA-DR 1限制性胶原特异性TCR的双转基因小鼠，以获得大量可用于免疫学研究的抗原特异性T细胞。在体外，来自该小鼠的CII特异性T细胞响应CII免疫显性肽A2而剧烈增殖，并且细胞改变了其表型，主要成为CD 62 Llow和CD 44 high“活化”T细胞。该反应伴随着Th 1、Th 2和Th 17型细胞因子的产生。用牛CII/CFA免疫后，与单转基因HLA-DR 1小鼠相比，这些小鼠发展加速的关节炎。另一方面，当小鼠口服类似肽A12（我们先前描述的胶原蛋白的抑制性类似物）时，关节炎被显著抑制，尽管事实上>90%的CD 4 + T细胞表达TCR Tg。在取自A12处理小鼠的GALT组织中，针对自身免疫胶原决定簇的IL-2、IFN-γ和IL-17的产生下降，而产生高水平的IL-10和IL-4。我们已经开发了一个人源化的自身免疫性关节炎模型，这将是有用的T细胞定向治疗的研究，以及T细胞介导的自身免疫性疾病的机制。
T cells orchestrate joint inflammation in rheumatoid arthritis (RA), yet they are difficult to study due to the small numbers of antigen-specific cells. The goal of this study was to characterize a new humanized model of autoimmune arthritis and to describe the phenotypic and functional changes that occur in autoimmune T cells following the induction of pathological events. We developed a double transgenic mouse containing both the HLA-DR1 transgene and an HLA-DR1-restricted collagen-specific TCR in order to obtain large numbers of antigen-specific T cells that can be used for immunologic studies. In vitro, CII-specific T cells from this mouse proliferated vigorously in response to the CII immunodominant peptide A2 and the cells altered their phenotype to become predominately CD62Llow and CD44high “activated” T cells. The response was accompanied by the production of Th1, Th2, and Th17-type cytokines. Following immunization with bovine CII/CFA, these mice develop an accelerated arthritis compared to single transgenic HLA-DR1 mice. On the other hand, when the mice were treated orally with the analog peptide A12, (a suppressive analog of collagen we have previously described), arthritis was significantly suppressed, despite the fact that >90% of the CD4+ T cells express the TCR Tg. In GALT tissues taken from the A12-treated mice, IL-2, IFN-γ, and IL-17 production to the autoimmune collagen determinant dropped while high levels of IL-10 and IL-4 were produced. We have developed a humanized model of autoimmune arthritis that will be useful for the study of T cell directed therapies as well as T cell mediated mechanisms of autoimmune diseases.
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影响因子：
--
作者：
Myers, Linda K.;Cullins, David L.;Brand, David D.;Kleinau, Sandra;Stuart, John M.;Kang, Andrew H.
通讯作者：
Kang, Andrew H.
影响因子：
3.7
作者：
Gong Y;Wang Z;Liang Z;Duan H;Ouyang L;Yu Q;Xu Z;Shen G;Weng X;Wu X
通讯作者：
Wu X
影响因子：
--
作者：
He, XW;Rosloniec, EF;Stuart, JM
通讯作者：
Stuart, JM
影响因子：
3.9
作者：
Iannone, Florenzo;Lapadula, Giovanni
通讯作者：
Lapadula, Giovanni
影响因子：
--
作者：
YOSHINO, S;QUATTROCCHI, E;WEINER, HL
通讯作者：
WEINER, HL